Early oseltamivir associated with improved influenza outcomes in hospitalized children

1. In a large retrospective cohort of hospitalized children with influenza, those who received oseltamivir within one day of admission had significantly shorter length of stay and lower 7-day readmission rates.

2. Early oseltamivir treatment was also associated with lower risk of severe outcomes, including a 59% decrease in odds of intensive care unit (ICU) transfer.

Evidence Rating Level: 2 (Good)

Study Rundown: Seasonal influenza causes significant morbidity in children. Oseltamivir, an antiviral medication, has been routinely used to treat pediatric influenza for more than a decade, but data in hospitalized children remain somewhat limited. This multicenter retrospective cohort study aimed to assess early use of oseltamivir in this population. Among about 56,000 children, 59.5% were treated with oseltamivir by the end of the first day of admission. Children who received early oseltamivir had a significant one-day decrease in median length of stay, 28% lower odds of 7-day readmission, 59% lower odds of late intensive care unit (ICU) transfer, and 37% lower odds of mortality or extracorporeal membrane oxygenation (ECMO) use than those who did not. These differences in outcomes remained significant in subgroups of children with complex chronic conditions and early ICU admission. Significant differences persisted across age groups and for children with a history of asthma, except that rates of in-hospital death or ECMO use did not differ significantly for children aged 2-5 or children with asthma. This study supports the existing consensus on oseltamivir use for pediatric influenza and strengthens evidence on inpatient use, including for high-risk patients. Though a robust weighted model was used to account for underlying differences between children who did and did not receive oseltamivir, randomized controlled trials in inpatient subgroups of interest would provide valuable additional insight. The 59.5% rate of early treatment with oseltamivir between 2007 and 2020 suggests current underuse of beneficial antiviral therapy in hospitalized children.

Click to read the study in JAMA Pediatrics

Relevant Reading: Influenza in children

In-Depth [retrospective cohort]: Children treated as inpatients at 36 tertiary care centers between 2007 and 2020 with diagnostic codes for influenza recorded were included. Only one encounter per patient per influenza season was included, and encounters with discharge, death, or ECMO use within one day of admission were excluded. Late ICU transfer occurred in 3.7% of patients, and in-hospital death or ECMO use in 1.1%. Propensity scores were calculated for each patient using multivariable linear mixed effects models including age, sex, race, primary insurance, the presence of complex chronic conditions, and asthma history. Inverse probability treatment weighted analysis was performed with weighting by propensity score. Based on this analysis, median length of stay was 3 days in the early oseltamivir group and 4 days in the untreated group with an adjusted odds ratio of 0.52 [95% confidence interval (CI) 0.52-0.53]. The rate of either death or ECMO use was 0.9% in the early oseltamivir group and 1.4% in the untreated group (adjusted odds ratio 0.63, 95% CI 0.54-0.73).

Image: PD

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